Hydroxychloroquine or Diltiazem-Niclosamide for the Treatment of COVID-19

NCT ID: NCT04372082

Last Updated: 2021-03-11

Basic Information

• Recruitment Status: WITHDRAWN
• Clinical Phase: PHASE3
• Study Classification: INTERVENTIONAL
• Study Start Date: 2020-05-31
• Study Completion Date: 2023-05-31

Brief Summary

No optimal antiviral intervention has been yet validated to treat COVID-19 disease. Comorbidities, such as older age, obesity, diabetes, history of cardiovascular diseases are associated with poor prognosis.

This study aims to evaluate the efficacy of two experimental antiviral treatments, compared to standard of care (SOC), to prevent clinical worsening, hospitalization or death at day 14 in adults with documented SARS-CoV-2 infection, asymptomatic or with symptoms lasting less than 8 days, and associated comorbidities without any severity criteria of the disease at inclusion.

Participants will be randomized to receive SOC alone or SOC + hydroxychloroquine 200 mg three times a day during 10 days or SOC + association of niclosamide 2 g at J1 then 500 mg two times a day with diltiazem 60 mg three times a day during 10 days. Efficacy and tolerance of each treatments will be compared across the three treatment groups during the 28 days of follow-up.

Conditions

Sars-CoV2

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: SINGLE

Study Groups

standard of care (SOC)

Group Type: PLACEBO_COMPARATOR

Standard of care (SOC)

Intervention Type: OTHER

SOC procedures including self-monitoring and medical follow-up of clinical signs and if necessary any other symptomatic treatment (paracetamol, antibiotics, steroids, oxygen…) during the whole study duration

SOC + Hydroxychloroquine

Group Type: EXPERIMENTAL

Standard of care (SOC)

Intervention Type: OTHER

SOC procedures including self-monitoring and medical follow-up of clinical signs and if necessary any other symptomatic treatment (paracetamol, antibiotics, steroids, oxygen…) during the whole study duration

Hydroxychloroquine

Intervention Type: DRUG

200 mg x 3 per day during 10 days in addition to SOC

SOC + Diltiazem-Niclosamide

Group Type: EXPERIMENTAL

Standard of care (SOC)

Intervention Type: OTHER

SOC procedures including self-monitoring and medical follow-up of clinical signs and if necessary any other symptomatic treatment (paracetamol, antibiotics, steroids, oxygen…) during the whole study duration

Association of diltiazem and niclosamide

Intervention Type: DRUG

niclosamide 500 mg x 4 at J1 then 500 mg x 2 per day + diltiazem 60 mg x 3 per day during 10 days in addition to SOC

Interventions

Standard of care (SOC)

SOC procedures including self-monitoring and medical follow-up of clinical signs and if necessary any other symptomatic treatment (paracetamol, antibiotics, steroids, oxygen…) during the whole study duration

Intervention Type: OTHER

Hydroxychloroquine

200 mg x 3 per day during 10 days in addition to SOC

Intervention Type: DRUG

Association of diltiazem and niclosamide

niclosamide 500 mg x 4 at J1 then 500 mg x 2 per day + diltiazem 60 mg x 3 per day during 10 days in addition to SOC

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• Positive SARS-CoV-2 test on nasopharyngeal swab
• Onset of symptoms <8 days prior to randomization
• NEWS score<4 AND no item ≥2
• At least one comorbidity among: age ≥ 70 years old, history of cardiac disease, diabetes, obesity, chronic kidney disease, chronic respiratory failure, immunosuppression, neoplasia, liver failure (stage ≥ Child-Pugh B)
• Fully able to understand the challenges of the trial
• Signed informed consent
• Covered by Health Insurance

Exclusion Criteria

For all patients:

• Inability to decide to participate
• Pregnancy or breath feeding
• Hypersensitivity to any of the test drugs
• stage 4 or 5 chronic kidney disease (DFG <30 mL/min/1.73 m²)

For hydroxychloroquine arm:

• Long QT syndrome or QTc space >500 ms
• Treatment with piperazine, halofantrine, dasatinib, nilotinib, citalopram, escitalopram, hydroxyzine, domperidone
• Hepatic porphyria, retinopathy, known glucose-6-phosphate dehydrogenase deficiency,
• Heart rate <50/min
• hypokaliemia < 3.5 mmol/L

For diltiazem arm:

• Heart rate<40/min
• Sinus bradycardia, second- or third-degree atrioventricular block
• Left heart insufficiency with pulmonary stasis
• Treatment with dantrolene, pimozide, dihydroergotamine, ergotamine, nifedipine, ivabradine, esmolol, bêta-blockers (bisoprolol, carvedilol, metoprolol, nebivolol), fingolimod

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

I-site University Lille North Europe

UNKNOWN

Sponsor Role: collaborator

University Hospital, Lille

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Karine Faure, MD,PhD

Role: PRINCIPAL_INVESTIGATOR

University Hospital, Lille

Other Identifiers

2020-002188-72

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

2020_40

Identifier Type: -

Identifier Source: org_study_id